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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
6 October 1983 to 11 November 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
- Principle of test:
The purpose of this acute intraperitoneal toxicity (LD50) study was to assess the toxicity of CME 134 when administered to rats by single intraperitoneal injection, followed by an observation period of 14 days.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea
EC Number:
617-441-5
Cas Number:
83121-18-0
Molecular formula:
C14 H6 Cl2 F4 N2 O2
IUPAC Name:
1-(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea
Test material form:
solid

Test animals

Species:
rat
Strain:
other: KFM: Wistar rat
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: males: 7 weeks, females: 9 weeks
- Weight at study initiation: males: 166 - 243 g, females: 160 - 196 g
- Housing: animals were housed in groups of 5 in makrolon type-3 cages with wire mesh lids
- Diet: ad libitum, pelleted standard Kliba 343, rat maintenance diet (Klingentalmuehle AG, CH 4303 Kaiseraugst/Switzerland)
- Water: ad libitum, tap water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
polyethylene glycol
Details on exposure:
The test substance dilution was intraperitoneally injected with a sterile needle and syringe into the abdominal cavity through the ventral abdominal wall in the inguinal region.
Doses:
Volume/kg body weight:
10 mL at 300 mg/kg bw
10 mL at 500 mg/kg bw
10 mL at 800 mg/kg bw
10 mL at 1200 mg/kg bw
10 mL at 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 and 21 days
- Frequency of observations and weighing: Mortality was confirmed and recorded 5 times during test day 1 and daily on test days 2 to 15, respectively 22 in the rats of the 1200 and 2000 mg/kg bw groups.
Each animal had an examination for changes in appearence and behavior 5 times during day 1, and daily during days 2 to 15, respectively 22 in the rats of the 1200 and 2000 mg/kg bw groups.
Body weights were recorded on test days 1, 8 and 15, respectively 22 in the rats of the 1200 and 2000 mg/kg bw groups.
- Necropsy of survivors performed: yes
Statistics:
The LOGIT Model could not be applied to the observed rates of death. The LD50 was estimated without use of a statistical model.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The following death rates were observed:
10% at 300 mg/kg,
30% at 500 mg/kg,
20% at 800 mg/kg,
0% at 1200 mg/kg,
20% at 2000 mg/kg
Clinical signs:
The following symptoms were observed:

15-day observation period:
300, 500 and 800 mg/kg bw: sedation, dyspnea, ataxia, curved body position, ruffled fur. Signs were resolved in surviving rats within 6 days (300 mg/kg bw), 7 days (500 mg/kg bw) or 11 days (800 mg/kg bw).

22-day observation period:
1200 mg/kg, males: sedation, dyspnea, ataxia, ventral and curved body position, ruffled fur. The surviving rats had recovered within 12 observation days.
1200 mg/kg, females: sedation, dyspnea, ataxia, curved body position, diarrhea, weight loss, ruffled fur. The surviving rats had not completely recovered at termination of the observation period.

2000 mg/kg, males: sedation, dyspnea, ataxia, ventral- and curved body position, ruffled fur. The surviving rats had recovered within 12 observation days.
2000 mg/kg, females: sedation, dyspnea, ataxia, curved body position, diarrhea, weight loss, ruffled fur. The surviving rats had not completely recovered at termination of the observation period.
Body weight:
500 mg/kg bw, males: loss of body weight between Day 1 and 8.
2000 mg/kg bw, males: loss of body weight between Day 1 and 8.

1200 mg/kg bw, females: loss of body weight between Day 1 and 15.
2000 mg/kg bw, females: loss of body weight between Day 1 and 15.
Gross pathology:
In several rats, remainders of the test substance were found in the abdominal cavity. These remainders were found posterior to sternum in most rats. Peritonitis characterized by adhesions of liver to diaphragm, of liver lobes, and/or of intestinal loops was seen in all rats. The abdominal organs were covered by grey-white coatings.

Applicant's summary and conclusion